메뉴 건너뛰기




Volumn 71, Issue 2, 2011, Pages 424-434

IL-6 trans-signaling in formation and progression of malignant ascites in ovarian cancer

Author keywords

[No Author keywords available]

Indexed keywords

2 (2 AMINO 3 METHOXYPHENYL)CHROMONE; CADHERIN; INTERLEUKIN 6 RECEPTOR ALPHA; MITOGEN ACTIVATED PROTEIN KINASE; PROTEIN TYROSINE KINASE; TAXANE DERIVATIVE;

EID: 78751549236     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-10-1496     Document Type: Article
Times cited : (157)

References (47)
  • 2
    • 0025175532 scopus 로고
    • Constitutive production of interleukin 6 by ovarian cancer cell lines and by primary ovarian tumor cultures
    • Watson JM, Sensintaffar JL, Berek JS, Martinez-Maza O. Constitutive production of interleukin 6 by ovarian cancer cell lines and by primary ovarian tumor cultures. Cancer Res 1990;50:6959-65.
    • (1990) Cancer Res , vol.50 , pp. 6959-6965
    • Watson, J.M.1    Sensintaffar, J.L.2    Berek, J.S.3    Martinez-Maza, O.4
  • 3
    • 0028871101 scopus 로고
    • Prognostic significance of interleukin 6 serum levels in patients with ovarian cancer
    • Scambia G, Testa U, Benedetti Panici P, et al. Prognostic significance of interleukin 6 serum levels in patients with ovarian cancer. Br J Cancer 1995;71:354-6.
    • (1995) Br J Cancer , vol.71 , pp. 354-356
    • Scambia, G.1    Testa, U.2    Benedetti Panici, P.3
  • 5
    • 0029084805 scopus 로고
    • Interleukin-6 family of cytokines and gp130
    • Kishimoto T, Akira S, Narazaki M, Taga T. Interleukin-6 family of cytokines and gp130. Blood 1995;86:1243-54.
    • (1995) Blood , vol.86 , pp. 1243-1254
    • Kishimoto, T.1    Akira, S.2    Narazaki, M.3    Taga, T.4
  • 6
    • 0037123348 scopus 로고    scopus 로고
    • Reproductive hormoneinduced, STAT3-mediated interleukin 6 action in normal and malignant human ovarian surface epithelial cells
    • Syed V, Ulinski G, Mok SC, Ho SM. Reproductive hormoneinduced, STAT3-mediated interleukin 6 action in normal and malignant human ovarian surface epithelial cells. J Natl Cancer Inst 2002; 94:617-29.
    • (2002) J Natl Cancer Inst , vol.94 , pp. 617-629
    • Syed, V.1    Ulinski, G.2    Mok, S.C.3    Ho, S.M.4
  • 7
    • 0031049172 scopus 로고    scopus 로고
    • Effects of interleukin-6 on in vitro cell attachment, migration and invasion of human ovarian carcinoma
    • Obata NH, Tamakoshi K, Shibata K, Kikkawa F, Tomoda Y. Effects of interleukin-6 on in vitro cell attachment, migration and invasion of human ovarian carcinoma. Anticancer Res 1997;17:337-42.
    • (1997) Anticancer Res , vol.17 , pp. 337-342
    • Obata, N.H.1    Tamakoshi, K.2    Shibata, K.3    Kikkawa, F.4    Tomoda, Y.5
  • 8
    • 0028226196 scopus 로고
    • Soluble receptors for cytokines and growth factors: Generation and biological function
    • Rose-John S, Heinrich PC. Soluble receptors for cytokines and growth factors: generation and biological function. Biochem J 1994;300:281-90.
    • (1994) Biochem J , vol.300 , pp. 281-290
    • Rose-John, S.1    Heinrich, P.C.2
  • 9
    • 0032533949 scopus 로고    scopus 로고
    • Interleukin-6 and soluble interleukin- 6 receptor: Direct stimulation of gp130 and hematopoiesis
    • Peters M, Muller AM, Rose-John S. Interleukin-6 and soluble interleukin- 6 receptor: direct stimulation of gp130 and hematopoiesis. Blood 1998;92:3495-504.
    • (1998) Blood , vol.92 , pp. 3495-3504
    • Peters, M.1    Muller, A.M.2    Rose-John, S.3
  • 10
    • 0030891228 scopus 로고    scopus 로고
    • Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment
    • Romano M, Sironi M, Toniatti C, Polentarutti N, Fruscella P, Ghezzi P, et al. Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment. Immunity 1997;6:315-25.
    • (1997) Immunity , vol.6 , pp. 315-325
    • Romano, M.1    Sironi, M.2    Toniatti, C.3    Polentarutti, N.4    Fruscella, P.5    Ghezzi, P.6
  • 11
    • 24744435772 scopus 로고    scopus 로고
    • Directing transition from innate to acquired immunity: Defining a role for IL-6
    • Jones SA. Directing transition from innate to acquired immunity: defining a role for IL-6. J Immunol 2005;175:3463-8.
    • (2005) J Immunol , vol.175 , pp. 3463-3468
    • Jones, S.A.1
  • 12
    • 38949164424 scopus 로고    scopus 로고
    • Transgenic blockade of interleukin 6 transsignaling abrogates inflammation
    • Rabe B, Chalaris A, May U, Waetzig GH, Seegert D, Williams AS, et al. Transgenic blockade of interleukin 6 transsignaling abrogates inflammation. Blood 2008;111:1021-8.
    • (2008) Blood , vol.111 , pp. 1021-1028
    • Rabe, B.1    Chalaris, A.2    May, U.3    Waetzig, G.H.4    Seegert, D.5    Williams, A.S.6
  • 13
    • 0034960582 scopus 로고    scopus 로고
    • Il-6 and its soluble receptor orchestrate a temporal switch in the pattern of leukocyte recruitment seen during acute inflammation
    • Hurst SM, Wilkinson TS, McLoughlin RM, Jones S, Horiuchi S, Yamamoto N, et al. Il-6 and its soluble receptor orchestrate a temporal switch in the pattern of leukocyte recruitment seen during acute inflammation. Immunity 2001;14:705-14.
    • (2001) Immunity , vol.14 , pp. 705-714
    • Hurst, S.M.1    Wilkinson, T.S.2    McLoughlin, R.M.3    Jones, S.4    Horiuchi, S.5    Yamamoto, N.6
  • 14
    • 0042834261 scopus 로고    scopus 로고
    • Soluble IL-6 receptor governs IL-6 activity in experimental arthritis: Blockade of arthritis severity by soluble glycoprotein 130
    • Nowell MA, Richards PJ, Horiuchi S, Yamamoto N, Rose-John S, Topley N, et al. Soluble IL-6 receptor governs IL-6 activity in experimental arthritis: blockade of arthritis severity by soluble glycoprotein 130. J Immunol 2003;171:3202-9.
    • (2003) J Immunol , vol.171 , pp. 3202-3209
    • Ma, N.1    Richards, P.J.2    Horiuchi, S.3    Yamamoto, N.4    Rose-John, S.5    Topley, N.6
  • 15
    • 5644252874 scopus 로고    scopus 로고
    • TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling
    • Becker C, Fantini MC, Schramm C, Lehr HA, Wirtz S, Nikolaev A, et al. TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling. Immunity 2004;21:491-501.
    • (2004) Immunity , vol.21 , pp. 491-501
    • Becker, C.1    Fantini, M.C.2    Schramm, C.3    Lehr, H.A.4    Wirtz, S.5    Nikolaev, A.6
  • 16
    • 34548445119 scopus 로고    scopus 로고
    • The pathogenesis of malignant ascites
    • Tamsma J. The pathogenesis of malignant ascites. Cancer Treat Res 2007;134:109-18.
    • (2007) Cancer Treat Res , vol.134 , pp. 109-118
    • Tamsma, J.1
  • 17
    • 25644449640 scopus 로고    scopus 로고
    • Pathophysiological consequences of VEGFinduced vascular permeability
    • Weis SM, Cheresh DA. Pathophysiological consequences of VEGFinduced vascular permeability. Nature 2005;437:497-504.
    • (2005) Nature , vol.437 , pp. 497-504
    • Weis, S.M.1    Cheresh, D.A.2
  • 18
    • 0031719516 scopus 로고    scopus 로고
    • Role of vascular endothelial growth factor in ovarian cancer: Inhibition of ascites formation by immunoneutralization
    • Mesiano S, Ferrara N, Jaffe RB. Role of vascular endothelial growth factor in ovarian cancer: inhibition of ascites formation by immunoneutralization. Am J Pathol 1998;153:1249-56.
    • (1998) Am J Pathol , vol.153 , pp. 1249-1256
    • Mesiano, S.1    Ferrara, N.2    Jaffe, R.B.3
  • 19
    • 28244475975 scopus 로고    scopus 로고
    • Interleukin-6, secreted by human ovarian carcinoma cells, is a potent proangiogenic cytokine
    • Nilsson MB, Langley RR, Fidler IJ. Interleukin-6, secreted by human ovarian carcinoma cells, is a potent proangiogenic cytokine. Cancer Res 2005;65:10794-800.
    • (2005) Cancer Res , vol.65 , pp. 10794-10800
    • Nilsson, M.B.1    Langley, R.R.2    Fidler, I.J.3
  • 21
    • 55249092252 scopus 로고    scopus 로고
    • Structure-guided optimization of the interleukin-6 transsignaling antagonist sgp130
    • Tenhumberg S, Waetzig GH, Chalaris A, Rabe B, Seegert D, Scheller J, et al. Structure-guided optimization of the interleukin-6 transsignaling antagonist sgp130. J Biol Chem 2008;283:27200-7.
    • (2008) J Biol Chem , vol.283 , pp. 27200-27207
    • Tenhumberg, S.1    Waetzig, G.H.2    Chalaris, A.3    Rabe, B.4    Seegert, D.5    Scheller, J.6
  • 22
    • 33750615143 scopus 로고    scopus 로고
    • Methods to assess tissue permeability
    • Ibla JC, Khoury J. Methods to assess tissue permeability. Methods Mol Biol 2006;341:111-7.
    • (2006) Methods Mol Biol , vol.341 , pp. 111-117
    • Ibla, J.C.1    Khoury, J.2
  • 23
    • 13244291368 scopus 로고    scopus 로고
    • Arsenic trioxide prevents radiation-enhanced tumor invasiveness and inhibits matrix metalloproteinase-9 through downregulation of nuclear factor kappaB
    • Wei LH, Lai KP, Chen CA, Cheng CH, Huang YJ, Chou CH, et al. Arsenic trioxide prevents radiation-enhanced tumor invasiveness and inhibits matrix metalloproteinase-9 through downregulation of nuclear factor kappaB. Oncogene 2005;24:390-8.
    • (2005) Oncogene , vol.24 , pp. 390-398
    • Wei, L.H.1    Kp, L.2    Chen, C.A.3    Ch, C.4    Huang, Y.J.5    Ch, C.6
  • 24
    • 0028203595 scopus 로고
    • Interleukin-6 level in serum and ascites as a prognostic factor in patients with epithelial ovarian cancer
    • Plante M, Rubin SC, Wong GY, Federici MG, Finstad CL, Gastl GA. Interleukin-6 level in serum and ascites as a prognostic factor in patients with epithelial ovarian cancer. Cancer 1994;73:1882-8.
    • (1994) Cancer , vol.73 , pp. 1882-1888
    • Plante, M.1    Rubin, S.C.2    Wong, G.Y.3    Federici, M.G.4    Finstad, C.L.5    Gastl, G.A.6
  • 25
    • 7444269580 scopus 로고    scopus 로고
    • Antiangiogenic activity of paclitaxel is associated with its cytostatic effect, mediated by the initiation but not completion of a mitochondrial apoptotic signaling pathway
    • Pasquier E, Carre M, Pourroy B, Camoin L, Rebai O, Briand C, et al. Antiangiogenic activity of paclitaxel is associated with its cytostatic effect, mediated by the initiation but not completion of a mitochondrial apoptotic signaling pathway. Mol Cancer Ther 2004;3:1301-10.
    • (2004) Mol Cancer Ther , vol.3 , pp. 1301-1310
    • Pasquier, E.1    Carre, M.2    Pourroy, B.3    Camoin, L.4    Rebai, O.5    Briand, C.6
  • 26
    • 1842632667 scopus 로고    scopus 로고
    • Endothelial cell-cell junctions: Happy together
    • Dejana E. Endothelial cell-cell junctions: happy together. Nat Rev Mol Cell Biol 2004;5:261-70.
    • (2004) Nat Rev Mol Cell Biol , vol.5 , pp. 261-270
    • Dejana, E.1
  • 27
    • 48649101326 scopus 로고    scopus 로고
    • Endothelial adherens junctions control tight junctions by VEcadherin- mediated upregulation of claudin-5
    • Taddei A, Giampietro C, Conti A, Orsenigo F, Breviario F, Pirazzoli V, et al. Endothelial adherens junctions control tight junctions by VEcadherin- mediated upregulation of claudin-5. Nat Cell Biol 2008;10: 923-34.
    • (2008) Nat Cell Biol , vol.10 , pp. 923-934
    • Taddei, A.1    Giampietro, C.2    Conti, A.3    Orsenigo, F.4    Breviario, F.5    Pirazzoli, V.6
  • 28
    • 33847050140 scopus 로고    scopus 로고
    • Src kinase phosphorylates vascular endothelial-cadherin in response to vascular endothelial growth factor: Identification of tyrosine 685 as the unique target site
    • Wallez Y, Cand F, Cruzalegui F, Wernstedt C, Souchelnytskyi S, Vilgrain I, et al. Src kinase phosphorylates vascular endothelial-cadherin in response to vascular endothelial growth factor: identification of tyrosine 685 as the unique target site. Oncogene 2007;26:1067-77.
    • (2007) Oncogene , vol.26 , pp. 1067-1077
    • Wallez, Y.1    Cand, F.2    Cruzalegui, F.3    Wernstedt, C.4    Souchelnytskyi, S.5    Vilgrain, I.6
  • 29
    • 0035160256 scopus 로고    scopus 로고
    • Soluble gp130 is the natural inhibitor of soluble interleukin-6 receptor transsignaling responses
    • Jostock T, Mullberg J, Ozbek S, Atreya R, Blinn G, Voltz N, et al. Soluble gp130 is the natural inhibitor of soluble interleukin-6 receptor transsignaling responses. Eur J Biochem 2001;268:160-7.
    • (2001) Eur J Biochem , vol.268 , pp. 160-167
    • Jostock, T.1    Mullberg, J.2    Ozbek, S.3    Atreya, R.4    Blinn, G.5    Voltz, N.6
  • 30
    • 0037180757 scopus 로고    scopus 로고
    • Inflammation and cancer
    • Coussens LM, Werb Z. Inflammation and cancer. Nature 2002; 420:860-7.
    • (2002) Nature , vol.420 , pp. 860-867
    • Coussens, L.M.1    Werb, Z.2
  • 31
    • 4344637470 scopus 로고    scopus 로고
    • Peritoneal inflammation - A microenvironment for Epithelial Ovarian Cancer (EOC)
    • Freedman RS, Deavers M, Liu J, Wang E. Peritoneal inflammation - A microenvironment for Epithelial Ovarian Cancer (EOC). J Transl Med 2004;2:23.
    • (2004) J Transl Med , vol.2 , pp. 23
    • Freedman, R.S.1    Deavers, M.2    Liu, J.3    Wang, E.4
  • 32
    • 33747502769 scopus 로고    scopus 로고
    • Monocyte/macrophage and T-cell infiltrates in peritoneum of patients with ovarian cancer or benign pelvic disease
    • Wang X, Deavers M, Patenia R, Bassett RL Jr, Mueller P, Ma Q, et al. Monocyte/macrophage and T-cell infiltrates in peritoneum of patients with ovarian cancer or benign pelvic disease. J Transl Med 2006;4:30.
    • (2006) J Transl Med , vol.4 , pp. 30
    • Wang, X.1    Deavers, M.2    Patenia, R.3    Bassett Jr., R.L.4    Mueller, P.5    Ma, Q.6
  • 33
    • 34548856204 scopus 로고    scopus 로고
    • Apoptosis is a natural stimulus of IL6R shedding and contributes to the proinflammatory trans-signaling function of neutrophils
    • Chalaris A, Rabe B, Paliga K, Lange H, Laskay T, Fielding CA, et al. Apoptosis is a natural stimulus of IL6R shedding and contributes to the proinflammatory trans-signaling function of neutrophils. Blood 2007;110:1748-55.
    • (2007) Blood , vol.110 , pp. 1748-1755
    • Chalaris, A.1    Rabe, B.2    Paliga, K.3    Lange, H.4    Laskay, T.5    Fielding, C.A.6
  • 34
    • 0036984640 scopus 로고    scopus 로고
    • Role of angiogenesis in tumor growth and metastasis
    • Folkman J. Role of angiogenesis in tumor growth and metastasis. Semin Oncol 2002;29(6 Suppl 16):15-8.
    • (2002) Semin Oncol , vol.29 , Issue.6 SUPPL. 16 , pp. 15-18
    • Folkman, J.1
  • 35
    • 0038105608 scopus 로고    scopus 로고
    • Inhibition of endothelial cell function in vitro and angiogenesis in vivo by docetaxel (Taxotere): Association with impaired repositioning of the microtubule organizing center
    • Hotchkiss KA, Ashton AW, Mahmood R, Russell RG, Sparano JA, Schwartz EL. Inhibition of endothelial cell function in vitro and angiogenesis in vivo by docetaxel (Taxotere): association with impaired repositioning of the microtubule organizing center. Mol Cancer Ther 2002;1:1191-200.
    • (2002) Mol Cancer Ther , vol.1 , pp. 1191-1200
    • Hotchkiss, K.A.1    Ashton, A.W.2    Mahmood, R.3    Russell, R.G.4    Sparano, J.A.5    Schwartz, E.L.6
  • 36
    • 0842282637 scopus 로고    scopus 로고
    • Taxane-mediated antiangiogenesis in vitro: Influence of formulation vehicles and binding proteins
    • Ng SS, Figg WD, Sparreboom A. Taxane-mediated antiangiogenesis in vitro: influence of formulation vehicles and binding proteins. Cancer Res 2004;64:821-4.
    • (2004) Cancer Res , vol.64 , pp. 821-824
    • Ng, S.S.1    Figg, W.D.2    Sparreboom, A.3
  • 37
    • 33748992592 scopus 로고    scopus 로고
    • Signal transducers and activators of transcription 3 pathway activation in drug-resistant ovarian cancer
    • Duan Z, Foster R, Bell DA, Mahoney J, Wolak K, Vaidya A, et al. Signal transducers and activators of transcription 3 pathway activation in drug-resistant ovarian cancer. Clin Cancer Res 2006;12:5055-63.
    • (2006) Clin Cancer Res , vol.12 , pp. 5055-5063
    • Duan, Z.1    Foster, R.2    Bell, D.A.3    Mahoney, J.4    Wolak, K.5    Vaidya, A.6
  • 38
    • 0032711015 scopus 로고    scopus 로고
    • Discovery of differentially expressed genes associated with paclitaxel resistance using cDNA array technology: Analysis of interleukin (IL) 6, IL-8, and onocyte chemotactic protein 1 in the paclitaxel-resistant phenotype
    • Duan Z, Feller AJ, Penson RT, Chabner BA, Seiden MV. Discovery of differentially expressed genes associated with paclitaxel resistance using cDNA array technology: analysis of interleukin (IL) 6, IL-8, and onocyte chemotactic protein 1 in the paclitaxel-resistant phenotype. Clin Cancer Res 1999;5:3445-53.
    • (1999) Clin Cancer Res , vol.5 , pp. 3445-3453
    • Duan, Z.1    Feller, A.J.2    Penson, R.T.3    Chabner, B.A.4    Seiden, M.V.5
  • 39
    • 0039917633 scopus 로고    scopus 로고
    • Confluence of vascular endothelial cells induces cell cycle exit by inhibiting p42/p44 mitogen-activated protein kinase activity
    • Vinals F, Pouyssegur J. Confluence of vascular endothelial cells induces cell cycle exit by inhibiting p42/p44 mitogen-activated protein kinase activity. Mol Cell Biol 1999;19:2763-72.
    • (1999) Mol Cell Biol , vol.19 , pp. 2763-2772
    • Vinals, F.1    Pouyssegur, J.2
  • 40
    • 0036316243 scopus 로고    scopus 로고
    • Regulation of microvascular permeability by vascular endothelial growth factors
    • Bates DO, Hillman NJ, Williams B, Neal CR, Pocock TM. Regulation of microvascular permeability by vascular endothelial growth factors. J Anat 2002;200:581-97.
    • (2002) J Anat , vol.200 , pp. 581-597
    • Bates, D.O.1    Hillman, N.J.2    Williams, B.3    Neal, C.R.4    Pocock, T.M.5
  • 41
    • 0035179483 scopus 로고    scopus 로고
    • Pathogenesis of malignant ascites: Starling's law of capillary hemodynamics revisited
    • Tamsma JT, Keizer HJ, Meinders AE. Pathogenesis of malignant ascites: Starling's law of capillary hemodynamics revisited. Ann Oncol 2001;12:1353-7.
    • (2001) Ann Oncol , vol.12 , pp. 1353-1357
    • Tamsma, J.T.1    Keizer, H.J.2    Meinders, A.E.3
  • 42
    • 0031825437 scopus 로고    scopus 로고
    • Vascular endothelial growth factor induces VE-cadherin tyrosine phosphorylation in endothelial cells
    • Esser S, Lampugnani MG, Corada M, Dejana E, Risau W. Vascular endothelial growth factor induces VE-cadherin tyrosine phosphorylation in endothelial cells. J Cell Sci 1998;111:1853-65.
    • (1998) J Cell Sci , vol.111 , pp. 1853-1865
    • Esser, S.1    Lampugnani, M.G.2    Corada, M.3    Dejana, E.4    Risau, W.5
  • 43
    • 0036087205 scopus 로고    scopus 로고
    • Histamine stimulates phosphorylation of adherens junction proteins and alters their link to vimentin
    • Shasby DM, Ries DR, Shasby SS, Winter MC. Histamine stimulates phosphorylation of adherens junction proteins and alters their link to vimentin. Am J Physiol Lung Cell Mol Physiol 2002;282: L1330-8.
    • (2002) Am J Physiol Lung Cell Mol Physiol , vol.282
    • Shasby, D.M.1    Ries, D.R.2    Shasby, S.S.3    Winter, M.C.4
  • 44
    • 16344387691 scopus 로고    scopus 로고
    • Platelet-activating factor increases VE-cadherin tyrosine phosphorylation in mouse endothelial cells and its association with the PtdIns3'-kinase
    • Hudry-Clergeon H, Stengel D, Ninio E, Vilgrain I. Platelet-activating factor increases VE-cadherin tyrosine phosphorylation in mouse endothelial cells and its association with the PtdIns3'-kinase. FASEB J 2005;19:512-20.
    • (2005) FASEB J , vol.19 , pp. 512-520
    • Hudry-Clergeon, H.1    Stengel, D.2    Ninio, E.3    Vilgrain, I.4
  • 45
    • 45149123112 scopus 로고    scopus 로고
    • TLR4 signaling is coupled to SRC family kinase activation, tyrosine phosphorylation of zonula adherens proteins, and opening of the paracellular pathway in human lung microvascular endothelia
    • Gong P, Angelini DJ, Yang S, Xia G, Cross AS, Mann D, et al. TLR4 signaling is coupled to SRC family kinase activation, tyrosine phosphorylation of zonula adherens proteins, and opening of the paracellular pathway in human lung microvascular endothelia. J Biol Chem 2008;283:13437-49.
    • (2008) J Biol Chem , vol.283 , pp. 13437-13449
    • Gong, P.1    Angelini, D.J.2    Yang, S.3    Xia, G.4    Cross, A.S.5    Mann, D.6
  • 46
    • 33749485053 scopus 로고    scopus 로고
    • Regulation of transendothelial migration of colon cancer cells by E-selectin-mediated activation of p38 and ERK MAP kinases
    • Tremblay PL, Auger FA, Huot J. Regulation of transendothelial migration of colon cancer cells by E-selectin-mediated activation of p38 and ERK MAP kinases. Oncogene 2006;25: 6563-73.
    • (2006) Oncogene , vol.25 , pp. 6563-6573
    • Tremblay, P.L.1    Auger, F.A.2    Huot, J.3


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.